Cumulative cyclophosphamide dose and serum anti-Mullerian hormone levels in adolescent cancer survivors in Indonesia

  • Sri Mulatsih
  • Sarrah Ayuandari
  • Naafi Rizqi Rahmawati
  • Rizki Oktasari FKKMK UGM
  • Agung Dewanto
Keywords: Cyclophosphamide, AMH, Adolescent Cancer Patient, Menstrual Cycle


Background As both the prevalence and survival rates of cancer in children and adolescents has risen, longer-term effects of cancer treatment must be investigated. High-risk gonadotoxic chemotherapeutic agents such as cyclophosphamide may affect the ovarian reserve and impact female adolescent fertility. Anti-Mullerian hormone is a reliable marker to assess ovarian reserve.

Objective To assess for a possible correlation between the cumulative dose of cyclophosphamide and serum anti-Mullerian hormone (AMH) levels among adolescent cancer patients.

Methods This cross-sectional study included 12-18-year-old adolescent female cancer patients who had experienced menarche and received cyclophosphamide therapy. We recorded the patients’ full history, including menstrual history, computed the cumulative dose of cyclophosphamide received, and measured serum AMH levels. The correlation test was performed to evaluate for a possible correlation between the cumulative dose of cyclophosphamide and ovarian reserve as represented by AMH levels.

Results Out of 12 female adolescent cancer patients, three complained of disturbances in their menstrual cycles. Low levels of AMH (<1.5 ng/mL) were noted in five patients. Median cumulative cyclophosphamide dose was 1,000 mg/m2 (range 1,000 to 5,250 mg/m2). Cumulative cyclophosphamide dose was negatively correlated with serum AMH levels, but this correlation was not statistically significant (r=-0.316, P=0.318).

Conclusion This study has not been able to show a correlation between cumulative cyclophosphamide dose and serum AMH level. Regular evaluation of fertility and involvement of fertility team is recommended in adolescents receiving high-risk gonadotoxic chemotherapeutic agents.


1. Rodriguez-Galindo C, Friedrich P, Alcasabas P, Antillon F, Banavali S, Castillo L, et al. Toward the cure of all children with cancer through collaborative efforts: pediatric oncology as a global challenge. J Clin Oncol. 2015;33:3065–73. DOI:
2. Gunn ME, Lähdesmäki T, Malila N, Arola M, Grönroos M, Matomäki J, et al. Late morbidity in long-term survivors of childhood brain tumors: a nationwide registry-based study in Finland. Neuro Oncol. 2015;17:747–56. DOI:
3. Ozono S, Ishida Y, Honda M, Okamura J, Asami K, Maeda N, et al. General health status and late effects among adolescent and young adult survivors of childhood cancer in Japan. Jpn J Clin Oncol. 2014;44:932–40. DOI:
4. Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol. 2016;12:2333–44. DOI:
5. An Q, Fan CH, Xu SM. Current views of common pediatric cancers – an update. Eur Rev Med Pharmacol Sci. 2017;21(4 Suppl):20-4. PMID: 29165770.
6. Miyoshi Y, Yasuda K, Tachibana M, Yoshida H, Miyashita E, Miyamura T, et al. Longitudinal observation of serum anti-Müllerian hormone in three girls after cancer treatment. Clin Pediatr Endocrinol. 2016;25:119-26. DOI:
7. Barbakadze L, Kristesashvili J, Khonelidze N, Tsagareishvili G. The correlations of anti-mullerian hormone, follicle-stimulating hormone and antral follicle count in different age groups of infertile women. Int J Fertil Steril. 2015;8:393-8. DOI:
8. Ayuandari S, Dewanto A, Oktasari R, Rahmawati NR, Alma NA, Hamurajib KC, et al. Anti-Mullerian hormone and puberty development in girls and adolescents who underwent cancer treatment. Arch Gynecol Obstet. 2022;305:1581-6. DOI:
9. Kim J, You S. After cyclophosphamide exposure, granulosa cells recover their anti-müllerian hormone-producing ability but not their numbers. Cytometry A. 2021;99:807–13. DOI:
10. D’Avila ÂM, Biolchi V, Capp E, Corleta HVE. Age, anti-müllerian hormone, antral follicles count to predict amenorrhea or oligomenorrhea after chemotherapy with cyclophosphamide. J Ovarian Res. 2015;8:82. DOI:
11. Clowse MEB, Copland SC, Hsieh TC, Chow SC, Hoffman GS, Merkel PA, et al. Oral cyclophosphamide therapy diminishes ovarian reserve in women with granulomatosis with polyangiitis (Wegener’s). Arthritis Care Res (Hoboken). 2011;63:1777–81. DOI: 10.1002/acr.20605.
12. Force LM, Abdollahpour I, Advani SM, Agius D, Ahmadian E, Alahdab F, et al. The global burden of childhood and adolescent cancer in 2017: an analysis of the Global Burden of Disease Study 2017. Lancet Oncol. 2019;20:1211–25. DOI:
13. Myers MG, Doran NM, Trinidad DR, Wall TL, Klonoff EA. A prospective study of cigarette smoking initiation during college: Chinese and Korean American students. Health Psychol. 2009;28:448–56. DOI:
14. Hile S, Erickson SJ, Agee B, Annett RD. Parental stress predicts functional outcome in pediatric cancer survivors. Psychooncology. 2014;23:1157–64. DOI:
15. Poon LHJ, Yu CP, Peng L, Ewig CLY, Zhang H, Li CK, et al. Clinical ascertainment of health outcomes in Asian survivors of childhood cancer: a systematic review. J Cancer Surviv. 2019;13:374–96. DOI:
16. Oktay K, Bedoschi G, Pacheco F, Turan V, Emirdar V. First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery. Am J Obstet Gynecol. 2016;214:94.e1-9. DOI:
How to Cite
Mulatsih S, Ayuandari S, Rahmawati N, Oktasari R, Dewanto A. Cumulative cyclophosphamide dose and serum anti-Mullerian hormone levels in adolescent cancer survivors in Indonesia. PI [Internet]. 3Nov.2023 [cited 30Nov.2023];63(5). Available from:
Pediatric Hemato-Oncology
Received 2022-06-19
Accepted 2023-11-03
Published 2023-11-03